
1. Clin Exp Allergy. 2009 Nov;39(11):1764-73.

Component-resolved diagnosis of pollen allergy based on skin testing with
profilin, polcalcin and lipid transfer protein pan-allergens.

Barber D, de la Torre F, Lombardero M, Antépara I, Colas C, Dávila I, Tabar AI,
Vidal C, Villalba M, Salcedo G, Rodríguez R.

Departamento de I+D, ALK-Abelló, Madrid, Spain. domingo.barber@alk-abello.com

BACKGROUND: Allergy diagnosis needs to be improved in patients suffering from
pollen polysensitization due to the existence of possible confounding factors in 
this type of patients. OBJECTIVE: To evaluate new diagnostic strategies by
comparing skin responses to pan-allergens and conventional allergenic extracts
with specific IgE (sIgE) to purified allergen molecules. METHODS: One thousand
three hundred and twenty-nine pollen-allergic patients were diagnosed by a
combination of an in vitro method with a panel of 13 purified allergens,
including major allergens and pan-allergens, using a high-capacity screening
technology (ADVIA-Centaur) and skin prick test (SPT) to pan-allergens and
conventional extracts. RESULTS: There was a high concordance (kappa index)
between in vitro (sIgE to major allergens) and in vivo (SPT to conventional
extracts) methods in patients who were not sensitized to pan-allergens, but SPT
with conventional extracts failed to diagnose patients with sensitization to
pan-allergens. In patients who were simultaneously sensitized to polcalcins and
profilins, there was a duplication both in the number of sensitizations to major 
allergens and in the years of disease evolution. There was a statistical
association between sensitization to profilins and/or lipid transfer proteins and
food allergy (P<0.0001). CONCLUSION: The novel diagnostic strategy has proven to 
be a valuable tool in daily clinical practice. Introduction of routine SPT to
pan-allergens is a simple and feasible way of improving diagnostic efficacy.
Patients sensitized to pan-allergens should be tested by an adequate panel of
allergenic molecules in order to identify the allergens that are responsible for 
the allergic disease.

PMID: 19877313 [PubMed - in process]


2. Dev Dyn. 2009 Oct 29. [Epub ahead of print]

A co-dependent requirement of xBcl9 and Pygopus for embryonic body axis
development in Xenopus.

Kennedy MW, Cha SW, Tadjuidje E, Andrews PG, Heasman J, Kao KR.

The Terry Fox Cancer Research Labs, Memorial University of Newfoundland, St.
John's, Newfoundland, Canada.

The Wnt/beta-catenin transcriptional activation complex requires the adapter
protein Pygopus (Pygo), which links the basal transcription machinery to
beta-catenin, by its association with legless (Lgs)/ B-cell lymphoma-9 (Bcl9).
Pygo was shown to be required for development in vertebrates, but the role of
Lgs/Bcl9 is unknown. We identified an amphibian orthologue of Lgs/Bcl9, XBcl9,
which interacted biochemically with Xbeta-catenin and XPygo2. The body axis
promoting ability of Xbeta-catenin was diminished when residues required for its 
interaction with XBcl9 were mutated. In blastula embryos, XBcl9 was transiently
preferentially expressed in nuclei of dorsoanterior cells and ectopically
expressed XBcl9 required XPygo2 to localize to nuclei. Furthermore, while neither
XBcl9 nor XPygo2 alone affected development when ectopically expressed, both were
required to induce supernumerary axis and dorsal gene activation. Like XPygo2,
depletion of maternal XBcl9 alone caused dorsal defects. These results indicated 
an essential role of the Pygo-Bcl9 duet in vertebrate body axis formation.
Developmental Dynamics, 2009. (c) 2009 Wiley-Liss, Inc.

PMID: 19877304 [PubMed - as supplied by publisher]


3. J Clin Apher. 2009 Oct 29. [Epub ahead of print]

Thrombotic microangiopathy during peripheral blood stem cell mobilization.

Naina HV, Gertz MA, Elliott MA.

Division of Hematology, Department of Internal Medicine, Mayo Clinic, College of 
Medicine, Rochester, Minnesota.

Granulocyte colony-stimulating factor (GCSF) is currently the most widely used
cytokine for stem cell mobilization. There are few studies suggesting GCSF
administration may induce activation of both coagulation and endothelial cells
that could favor the developing of thrombotic events. We report a 58-year-old
female with vasculitis and renal impairment. She was found to have an underlying 
monoclonal gammopathy of unknown significance (MGUS). The monoclonal protein was 
felt to play a role in her underlying renal disease and peripheral neuropathy.
She was considered a candidate for peripheral blood stem cell transplantation to 
manage the monoclonal protein. During stem cell mobilization with GCSF, she
developed worsening of anemia; thrombocytopenia and worsening of renal function. 
She was diagnosed with thrombotic microangiopathy (TMA) which was successfully
treated with therapeutic plasma exchange and rituximab. It is possible that GCSF 
may have directly (activating endothelial cells) or indirectly (activation of
underlying autoimmune disorder) contributed to TMA in this patient. J. Clin.
Apheresis 2009. (c) 2009 Wiley-Liss, Inc.

PMID: 19877288 [PubMed - as supplied by publisher]


4. J Orthop Res. 2009 Oct 29. [Epub ahead of print]

Altered expression of sodium channel distribution in the dorsal root ganglion
after gradual elongation of rat sciatic nerves.

Ohno K, Yokota A, Hirofuji S, Kanbara K, Ohtsuka H, Kinoshita M.

Department of Orthopedic Surgery, Osaka Medical College, 2-7, Daigaku-machi,
Takatsuki 569-8686, Japan.

To elucidate the pathophysiological mechanisms underlying chronic nerve-stretch
injury, we gradually lengthened rat femurs by 15 mm at the rate of 0.5 mm/day
(group L, n = 13). The control groups comprised sham-operated (group S, n = 10)
and naive (group N, n = 8) rats. Immediately after the lengthening, we performed 
a conduction study on their sciatic nerves and harvested samples.
Electrophysiological and histological analyses showed mild conduction slowing and
axonal degeneration of unmyelinated fibers in group L rats. Altered mRNA
expression of the voltage-gated sodium channels in the dorsal root ganglion was
also observed. Tetrodotoxin-resistant (TTX-R) sodium-channel Nav1.8 mRNA
expression was significantly decreased and TTX-R sodium-channel Nav1.9 mRNA
expression showed a tendency to decrease when compared with the mRNA expressions 
in the control groups. However, tetrodotoxin-sensitive (TTX-S) sodium-channel
Nav1.3 mRNA expression remained unaltered. The immunohistochemical alteration of 
Nav1.8 protein expression was parallel to the results of the mRNA expression.
Previous studies involving neuropathic states have suggested that
pain/paresthesia is modulated by a subset of sodium channels, including
downregulation and/or upregulation of TTX-R and TTX-S sodium channels,
respectively. Our findings indicate that Nav1.8 downregulation may be one of the 
pathophysiological mechanisms involved in limb lengthening-induced neuropathy.
(c) 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J
Orthop Res.

PMID: 19877286 [PubMed - as supplied by publisher]


5. Hum Mutat. 2009 Oct 29. [Epub ahead of print]

Spectrum of PEX6 mutations in Zellweger syndrome spectrum patients.

Ebberink MS, Kofster J, Wanders RJ, Waterham HR.

University of Amsterdam, Academic Medical Center, Department of Clinical
Chemistry, Laboratory Genetic Metabolic Diseases, Amsterdam, the Netherlands.

The autosomal recessive Zellweger syndrome spectrum (ZSS) disorders comprise a
main subgroup of the peroxisome biogenesis disorders. The ZSS disorders can be
caused by mutations in any of 12 different currently identified PEX genes
resulting in severe, often lethal, multi-systemic disorders. Defects in the PEX6 
gene are the second most common cause for ZSS disorders. The encoded protein PEX6
belongs to the AAA ATPase family and contains two AAA cassettes and an AAA
protein family signature. The PEX6 gene consists of 17 exons and previously
mutations in the PEX6 gene were found to be scattered over all exons. We
developed a post-PCR high-resolution melting (HRM) curve assay to scan the PEX6
gene for potential sequence variations followed by selective sequencing to
identify these. We analyzed the PEX6 genes of 75 patients assigned to the PEX6
complementation group. We identified a total of 77 different mutations of which
47 mutations have not been reported previously, and 14 polymorphic variants. (c) 
2009 Wiley-Liss, Inc.

PMID: 19877282 [PubMed - as supplied by publisher]


6. Dev Dyn. 2009 Oct 29. [Epub ahead of print]

Planar cell polarity effector gene Fuzzy regulates cilia formation and Hedgehog
signal transduction in mouse.

Heydeck W, Zeng H, Liu A.

Department of Biology, Eberly College of Science, The Pennsylvania State
University, University Park, Pennsylvania.

Precise planar cell polarity (PCP) is critical for the development of multiple
organ systems in animals. A group of core-PCP proteins are recognized to play
crucial roles in convergent extension and other PCP-related processes in mammals.
However, the functions of another group of PCP-regulating proteins, the
PCP-effector proteins, are yet to be fully studied. In this study, the generation
and characterization of a mouse mutant for the PCP effector gene Fuzzy (Fuz) is
reported. Fuz homozygous mutants are embryonically lethal, with multiple defects 
including neural tube defects, abnormal dorsal/ventral patterning of the spinal
cord, and defective anterior/posterior patterning of the limb buds. Fuz mutants
also exhibit abnormal Hedgehog (Hh) signaling and inefficient proteolytic
processing of Gli3. Finally, a significant decrease in cilia was found in Fuz
homozygous mutants. In conclusion, Fuz plays an important role in cilia
formation, Hh signal transduction, and embryonic development in mammals.
Developmental Dynamics, 2009. (c) 2009 Wiley-Liss, Inc.

PMID: 19877275 [PubMed - as supplied by publisher]


7. Dev Dyn. 2009 Oct 29. [Epub ahead of print]

Dynamic patterning at the pylorus: Formation of an epithelial intestine-stomach
boundary in late fetal life.

Li X, Udager AM, Hu C, Qiao XT, Richards N, Gumucio DL.

Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, 
Michigan.

In the adult mouse, distinct morphological and transcriptional differences
separate stomach from intestinal epithelium. Remarkably, the epithelial boundary 
between these two organs is literally one cell thick. This discrete junction is
established suddenly and precisely at embryonic day (E) 16.5, by sharpening a
previously diffuse intermediate zone. In the present study, we define the dynamic
transcriptome of stomach, pylorus, and intestinal tissues between E14.5 and
E16.5. We show that establishment of this boundary is concomitant with the
induction of over a thousand genes in intestinal epithelium, and these gene
products provide intestinal character. Hence, we call this process
intestinalization. We identify specific transcription factors (Hnf4gamma,
Creb3l3, and Tcfec) and examine signaling pathways (Hedgehog and Wnt) that may
play a role in this process. Finally, we define a unique expression domain at the
pylorus itself and detect novel pylorus-specific patterns for the transcription
factor Gata3 and the secreted protein nephrocan. Developmental Dynamics, 2009.
(c) 2009 Wiley-Liss, Inc.

PMID: 19877272 [PubMed - as supplied by publisher]


8. Dev Dyn. 2009 Oct 29. [Epub ahead of print]

Postnatal lung development of rhesus monkey airways: Cellular expression of Clara
cell secretory protein.

Coppens JT, Plopper CG, Murphy SR, Van Winkle LS.

Department of Anatomy, Physiology and Cell Biology, University of California,
Davis, California.

Clara cell secretory protein (CCSP) is a protective lung protein that is believed
to have antioxidant, immunomodulatory, and anticarcinogenic properties. Evidence 
suggests that CCSP is involved in mitigating many lung disease states during
development including asthma. This study's rationale is to define the
distribution and abundance of CCSP in the airway epithelium of the rhesus monkey 
during postnatal lung development using carefully controlled site-specific
morphometric approaches in defined airway regions. Immunoreactive CCSP was found 
in nonciliated cells and mucous cells, including glands, throughout the airway
epithelium at all ages, with proximal and mid-level airways having the highest
labeling. Overall airway CCSP levels were low at 1 week and 1 month, doubled
between 1 and 3 months, and changed little from 3 months to 3 years. Thus, the
critical developmental window for CCSP expression to reach adult levels in the
rhesus conducting airways occurs between 1 and 3 months of age. Developmental
Dynamics, 2009. (c) 2009 Wiley-Liss, Inc.

PMID: 19877270 [PubMed - as supplied by publisher]


9. Liver Transpl. 2009 Oct 28;15(11):1613-1621. [Epub ahead of print]

A20 protects mice from lethal liver ischemia/reperfusion injury by increasing
peroxisome proliferator-activated receptor-alpha expression.

Ramsey HE, Da Silva CG, Longo CR, Csizmadia E, Studer P, Patel VI, Damrauer SM,
Siracuse JJ, Daniel S, Ferran C.

Division of Vascular Surgery and the Center for Vascular Biology Research,
Departments of Surgery and Medicine, Beth Israel Deaconess Medical Center,
Harvard Medical School, Boston, MA.

The nuclear factor-kappaB inhibitory protein A20 demonstrates hepatoprotective
abilities through combined antiapoptotic, anti-inflammatory, and
pro-proliferative functions. Accordingly, overexpression of A20 in the liver
protects mice from toxic hepatitis and lethal radical hepatectomy, whereas A20
knockout mice die prematurely from unfettered liver inflammation. The effect of
A20 on oxidative liver damage, as seen in ischemia/reperfusion injury (IRI), is
unknown. In this work, we evaluated the effects of A20 upon IRI using a mouse
model of total hepatic ischemia. Hepatic overexpression of A20 was achieved by
recombinant adenovirus (rAd.)-mediated gene transfer. Although only 10%-25% of
control mice injected with saline or the control rAd.beta galactosidase survived 
IRI, the survival rate reached 67% in mice treated with rAd.A20. This significant
survival advantage in rAd.A20-treated mice was associated with improved liver
function, pathology, and repair potential. A20-treated mice had significantly
lower bilirubin and aminotransferase levels, decreased hemorrhagic necrosis and
steatosis, and increased hepatocyte proliferation. A20 protected against liver
IRI by increasing hepatic expression of peroxisome proliferator-activated
receptor alpha (PPARalpha), a regulator of lipid homeostasis and of oxidative
damage. A20-mediated protection of hepatocytes from hypoxia/reoxygenation and
H(2)O(2)-mediated necrosis was reverted by pretreatment with the PPARalpha
inhibitor MK886. In conclusion, we demonstrate that PPARalpha is a novel target
for A20 in hepatocytes, underscoring its novel protective effect against
oxidative necrosis. By combining hepatocyte protection from necrosis and
promotion of proliferation, A20-based therapies are well-poised to protect livers
from IRI, especially in the context of small-for-size and steatotic liver grafts.
Liver Transpl 15:1613-1621, 2009. (c) 2009 AASLD.

PMID: 19877201 [PubMed - as supplied by publisher]


10. Laryngoscope. 2009 Oct 29. [Epub ahead of print]

Pediatric cholesteatoma and variants in the gene encoding connexin 26.

James AL, Chadha NK, Papsin BC, Stockley TL.

Department of Otolaryngology , The Hospital for Sick Children, Toronto, Ontario, 
Canada.

OBJECTIVES/HYPOTHESIS:: Connexin 26 is a gap junction protein encoded by the GJB2
gene. It is expressed in cholesteatoma, and mutations cause proliferative skin
disorders and sensorineural hearing loss (SNHL). Deletions of GJB6, which encodes
connexin 30, cause SNHL in a digenic manner with a heterozygous GJB2 mutation. We
hypothesize that GJB2 and GJB6 mutations might influence the development of
cholesteatoma. STUDY DESIGN:: Prospective observational study to identify GJB
mutations in pediatric cholesteatoma. METHODS:: Peripheral blood samples from 98 
children with cholesteatoma were screened for mutations in the GJB2 gene by
direct sequencing of the coding region (exon 2 and the intron/exon boundary).
Deletions of the GJB6 gene were tested using multiple ligation probe
amplification methods. GJB status was compared with other populations and patient
age and extent of cholesteatoma at presentation. RESULTS:: Fourteen children had 
at least one GJB2 variant (14%). Of these, three had two variants. Two of the
variants were neutral polymorphisms. One child with the GJB2 genotype
35delG/35delG also had SNHL. No correlation was found between GJB2 status and
patient age or cholesteatoma severity at presentation. No GJB6 deletions were
found. CONCLUSIONS:: GJB2 gene variants are present in a minority of children
with cholesteatoma, but may be more common than in normal populations. It is
conceivable that alterations of connexin 26 expression could contribute to the
multifactorial disease process in cholesteatoma by modifying the cell-to-cell
communication that is important in proliferation and migration of keratinocytes. 
Laryngoscope, 2009.

PMID: 19877196 [PubMed - as supplied by publisher]

